Principal Investigator / Author(s): Michael T. Kleinman

Contractor: University of California, Irvine (UC Irvine)

Contract Number: 05-342

The Children's Health Study (CHS), conducted by the University of Southern California, has reported significant associations between reduced lung function growth and exposures to nitrogen dioxide (NO2), acid vapor, ambient particles less than 2.5 microns in diameter (PM2.5), and elemental carbon. The primary objective of this study was to use an animal model to test the hypothesis that chronic PM2.5 exposure during the period of rapid lung growth and development can lead to reduced growth in pulmonary function that is related to oxidative stress and tissue injury. We studied changes in the development of the mouse lung and lung function during chronic exposure to concentrated ambient PM2.5 using a mouse model. The mice were exposed from 3 weeks to 11 weeks of age, i.e. after weaning to the point where the rate of lung growth is slowed. The study also evaluated whether observed deficits in lung function persisted for up to two weeks after exposure was terminated. Mice that were exposed to concentrated ambient fine particles (CAPs) for eight weeks had reduced pulmonary function, measured as increased respiratory resistance, that persisted for up to 2 weeks after the termination of exposure. We have preserved tissue, blood, and bronchoalveolar lavage fluid samples for later analyses to investigate the relationship between pulmonary function deficits and alterations in lung structure, biochemical mediators of oxidative stress and inflammation, as well as alteration in gene expression that might be associated with lung development. We also examined the associations between particle chemical composition, particle physical characteristics and particle concentrations and observed changes in pulmonary function. There were two sets of exposures; the first exposures were performed at "high" concentration (PM2.5, 243 μg/m3; number concentration, 93,000 particles/cc) and the second exposures were at "low" concentration, (PM2.5 56 μg/m3; particle number 83,000 particles/cc). Both studies produced significant increases in resistance. Particle mass concentrations in the low study were nearly 1/5th that in the high study, however the particle number concentrations were nearly the same, suggesting that high concentrations of ultrafine particles were present during both sets of exposures. There were methodological differences between the two sets of exposures; however the results suggest that the ultrafine components of PM2.5 may be more strongly associated with the observed decreases in resistance in the PM-exposed developing lung than are larger-sized particle components.